Mucositis is a pathological condition characterized by mucosal damage, ranging from mild inflammation to deep ulcerations and affecting one or more parts of the alimentary tract from the mouth to the anus. Mucositis usually occurs as an adverse effect of treatment of diseases such as cancer. As a result of cell death in reaction to chemotherapy, the mucosal lining of the alimentary track such as the mouth becomes thin, may be inflamed and ulcerated. Radiotherapy to the head and neck or to the pelvis or abdomen can also cause oral or gastrointestinal mucositis. Oral and gastrointestinal (GI) mucositis affects many patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation (HSCT). Oral mucositis is particularly profound and prolonged among HSCT recipients who receive total-body irradiation.
Treatment-induced mucositis is one of the most debilitating and troublesome side effects from cancer therapy and affects quality of patient's life. The usual presentation of oral mucositis includes erythema and/or ulceration of the mucosa. In severe cases, the patient is unable to eat the solid food and even unable to consume liquids as well, resulting in the need for total parenteral nutrition (TPN). Gastrointestinal mucositis usually presents with pain, bloating, diarrhea, nausea and vomiting. As a result, mucositis is associated with considerable morbidity, diminished quality of life as well as negative health and economic outcomes. In addition, mucositis may interfere with the regular administration and dosing of programmed treatment plans, thus affecting the outcome of cancer treatment.
Oral ulceration is a very common presentation of oral mucositis, occurring in association with many diseases and by many different mechanisms. Recurrent oral ulceration is a condition in which a break or an erosion in the mucous membrane occurs recurrently in the mouth. The underlying cause of recurrent oral ulceration remains unclear. However, family tendency, trauma, hormonal factors, food or drug hypersensitivity, emotional stress, chemotherapy, irradiation therapy, neutropenic conditions and autoimmune diseases are known to be predisposing conditions for recurrent oral ulceration. For example, it is known that recurrent aphthous stomatitis (RAS), systemic lupus erthematosus (SLE) and Behcet's disease (BD) cause recurrent oral ulceration.
Recurrent aphthous stomatitis (RAS) is the most common cause of mouth ulcers. Aphthae are painful oral lesions that appear as localized, round shallow ulceration with a grayish base. The pathogenesis of aphthous ulcers is not well defined. Although the cause of aphthous stomatitis is not entirely clear, it is speculated that it is caused by bacteria infection, viral infection or immune dysregulation. It is also known that hot food, wound in the mouth, fatigue or allergy may cause aphthous stomatitis or exacerbate it.
Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease, affecting many organs in the body such as skin, joint, kidney, lung and neuronal system. The exact cause of SLE is not known, but several factors such as genes, hormones and environment factors have been associated with SLE. Common symptoms of SLE include rash on cheeks and nose and mouth ulcers. SLE may also cause joint pain, kidney problems and depression.
Behcet's disease (BD) is a rare immune-mediated small-vessel systemic vasculitis that often presents with oral ulcers, genital ulcers and ocular problems. As a systemic disease, it can also affect many organs such as the gastrointestinal tract, pulmonary, musculoskeletal, cardiovascular and neurological systems. The most common symptoms include oral ulcers, genital ulcers, inflammation of the eye, skin lesions, and arthritis. The exact cause of SLE is not known, but several factors such as genetic factors and environment factors may be responsible for Behcet's disease.
To date, treatment of mucositis is mainly supportive. Oral hygiene is the mainstay of treatment. Currently, no approved preventive or therapeutic agent consistently prevents mucositis in all clinical settings. Palifermin, or human recombinant keratinocyte growth factor (KGF) significantly reduces the incidence, duration, and severity of oral mucositis in patients undergoing autologous HSCT and has been approved for use in patients with hematologic malignancies undergoing high-dose chemotherapy with or without concomitant total body irradiation, with autologous or allogeneic stem cell transplantation. Low-level laser therapy (LLLT) is another treatment that can reduce the severity of oral mucositis. It involves focusing low-energy lasers at affected tissue. LLLT is thought to work by stimulating certain cells that then help to speed up the healing process. In addition, two agents, Gelclair® and Zilactin®, are mucosal protectants that work by coating the mucosa, forming a protective barrier for exposed nerve endings. In clinical trials, these agents improved pain control and the ability to eat and speak Amifostine (Ethyol®), a drug that offers some protection against the damage to the mucosa caused by radiation, is approved by the FDA for patients receiving radiation therapy for cancers of the head and neck. Studies have demonstrated that Amifostine can reduce dry mouth and may prevent or lessen the degree of the mucositis. However, the measures to prevent or treat mucositis are inadequate and limited to the control of pain, infections, bleeding and nutrition. It would be desirable to have a new method for preventing or treating mucositis, especially in cancer patients.
Deer antler is a traditional Asian medicine that is widely used, prepared by drying uncornified antler of a deer (Cornu cervi). Deer antler has been acclaimed to have various medical effects such as growth- and development-promoting effects, promoting hematopoietic function, treating nervous breakdown, beneficial to cardiac insufficiency, improving the function of five viscera and six entrails, as described in the Dong-eui Bogam, a Korean medical book first published in 1613. In addition, deer antler has been known to have various medical effects such as boosting strength and endurance, improvement of myocardial motion, recovery from tiredness, enhancement of the immune system. Active ingredients of deer antler and their effects have been studied. For example, it has been reported that certain components of deer antler, including rac-1-palmitoyl-2-linoleoyl-3-acetylglycerol (PLAG) obtained from chloroform extracts of the deer antler, have growth-stimulating activities of hematopoietic stem cells and megakaryocytes (WO 99/26640). It has also been reported that monoacetyldiacylglycerol derivatives which are active components of the deer antlers are effective in treating autoimmune diseases, sepsis, cancers such as bile duct cancer, kidney cancer or malignant melanoma, and so on (WO 2005/112912).